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Crystal structure of unliganded human CD21 SCR1-SCR2 (Complement receptor type 2)
Structural highlights
DiseaseCR2_HUMAN Genetic variations in CR2 are associated with susceptibility to systemic lupus erythematosus type 9 (SLEB9) [MIM:610927. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex genetic basis. SLE is an inflammatory, and often febrile multisystemic disorder of connective tissue characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system.[1] Defects in CR2 are the cause of immunodeficiency, common variable, type 7 (CVID7) [MIM:614699. A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B cells is usually in the normal range, but can be low.[2] FunctionCR2_HUMAN Receptor for complement C3Dd, for the Epstein-Barr virus on human B-cells and T-cells and for HNRPU. Participates in B lymphocytes activation.[3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman complement receptor type 2 (CD21) is the cellular receptor for Epstein-Barr virus (EBV), a human tumor virus. The N-terminal two short consensus repeats (SCR1-SCR2) of the receptor interact with the EBV glycoprotein gp350/220 and also with the natural CD21 ligand C3d. Here we present the crystal structure of the CD21 SCR1-SCR2 fragment in the absence of ligand and demonstrate that it is able to bind EBV. Based on a functional analysis of wild-type and mutant CD21 and molecular modeling, we identify a likely region for EBV attachment and demonstrate that this region is not involved in the interaction with C3d. A comparison with the previously determined structure of CD21 SCR1-SCR2 in complex with C3d shows that, in both cases, CD21 assumes compact V-shaped conformations. However, our analysis reveals a surprising degree of flexibility at the SCR1-SCR2 interface, suggesting interactions between the two domains are not specific. We present evidence that the V-shaped conformation is induced by deglycosylation of the protein, and that physiologic glycosylation of CD21 would result in a more extended conformation, perhaps with additional epitopes for C3d binding. The crystal structure of human CD21: Implications for Epstein-Barr virus and C3d binding.,Prota AE, Sage DR, Stehle T, Fingeroth JD Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10641-6. Epub 2002 Jul 16. PMID:12122212[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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